In the United States, men who have sex with men (MSM) comprise the group most severely affected by the HIV epidemic: 61% of all new infections in 2009 occurred in this population. Black MSM experience an even more disproportionate burden of infections, with prevalence of 28% in contrast to 16% in White, non- Latino MSM. HIV-infected Black MSM are also more likely than White MSM to receive an HIV diagnosis at their first testing experience, suggesting that they are less likely than other group to benefit from HIV prevention and control services. Clearly, the reduction of HIV-related disparities in Black MSM is a national health priority, essential to the success of efforts to contol and prevent HIV/AIDS as articulated in the National HIV/AIDS Strategy. Pre-Exposure Prophylaxis (PrEP), which has been shown to reduce acquisition among MSM, could play a critical role in the next generation of combination prevention interventions. Before PrEP is scaled up on a national level, however, critical questions must be answered regarding both the community-level factors that will shape uptake of and adherence to PrEP among Black MSM and the optimal clinical package for delivering PrEP in a way that is both scalable and effective. There is, moreover, a relationship between the broader social needs and perceptions of Black MSM and that clinical care package, and so we propose a multi-method study that incorporates community-based ethnography and an intervention in a community primary care clinic. The community-based ethnographic research will consist of institutional mapping, key informant interviews, ethnographic interviews with a systematic ethnographic sample, participant observation, and analysis of material culture. Drawing on the concepts of social risk, life projects, and social networks, we will explore the structural and cultural factors that shape men's sexual relationships, health systems engagement, and knowledge attitudes and practices related to HIV prevention in general and PrEP in particular. Findings from the ethnographic research will provide urgently needed information regarding community-contextual factors relevant to designing combination prevention interventions that include PrEP, and will lay the groundwork for the randomized controlled trial for PrEP for Black MSM in a community-based clinic. The clinic-based research will randomize eligible HIV- negative Black MSM to an enhanced versus standard PrEP package of care and compare their effectiveness on adherence with PrEP and reduction in sexual risk behaviors. The RCT will generate critical information regarding the acceptability of PrEP for Black MSM in a community clinical context, adherence to PrEP under non-experimental conditions, health providers' experiences with PrEP, and the impact of PrEP on sexual risk practices. PUBLIC HEALTH RELEVANCE: Black Men who have sex with men (MSM) have among the highest rates of new HIV infections of any group in the United States, and developing effective HIV prevention interventions that work with this group is a critical element of the National HIV/AIDS Strategy. We propose to carry out community-based research that will explore factors relevant to how Black MSM might engage with PrEP, and then to conduct a study in a community primary care clinic to compare two packages for providing PrEP. Together these efforts will provide critical information for building more effective HIV prevention interventions or this at-risk population.